E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Diabetes Mellitus, Type 2 |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nutritional and Metabolic Diseases [C18] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10045242 |
E.1.2 | Term | Type II diabetes mellitus |
E.1.2 | System Organ Class | 10027433 - Metabolism and nutrition disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To confirm the efficacy of the insulin degludec/insulin aspart (IDegAsp) twice daily (BID) simple titration algorithm in controlling glycaemia with respect to change from baseline in glycosylated haemoglobin (HbA1c) after 26 weeks of treatment. |
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E.2.2 | Secondary objectives of the trial |
- To compare the efficacy of the IDegAsp BID simple titration algorithm versus IDegAsp BID stepwise titration algorithm after 26 weeks of treatment in terms of other measurements of glycaemic control
- To compare the safety of the IDegAsp BID simple titration algorithm versus IDegAsp BID stepwise titration algorithm after 26 weeks of treatment |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Age ≥ 18 years
- Type 2 diabetes (diagnosed clinically) for ≥ 24 weeks prior to Visit 2 (randomisation)
- Currently treated with IGlar and up to 3 OADs (metformin, DPP-4 inhibitor, sulphonylurea/glinide or alpha-glucosidase inhibitor) - All antidiabetic treatments should have been ongoing for ≥12 weeks prior to Visit 2 (randomisation) and doses should have been stable in this period of time
- HbA1c 7.0-10.0% (both inclusive) by central laboratory analysis
- Body mass index (BMI) ≤ 40 kg/m^2 |
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E.4 | Principal exclusion criteria |
- Treatment with glucagon-like peptide 1 (GLP-1) receptor agonists or thiazolidinediones (TZDs) both within the last 12 weeks prior to Visit 2 (randomisation)
- Stroke; heart failure New York Heart Association (NYHA) class III or IV; myocardial infarction; unstable angina pectoris; or coronary arterial bypass graft or angioplasty; all within the last 24 weeks prior to Visit 2 (randomisation)
- Uncontrolled or untreated severe hypertension defined as systolic blood pressure ≥ 180 mmHg and/or diastolic blood pressure ≥ 100 mmHg
- Recurrent severe hypoglycaemia (more than 1 severe hypoglycaemic event during last 12 months) or hypoglycaemic unawareness as judged by the investigator
- Life-threatening disease (e.g. cancer) |
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E.5 End points |
E.5.1 | Primary end point(s) |
Change from baseline in HbA1c (%) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
After 26 weeks of treatment |
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E.5.2 | Secondary end point(s) |
Key secondary efficacy endpoints:
1. Change from baseline in fasting plasma glucose (FPG)
2. Subjects achieving HbA1c targets:
* Proportion of subjects with HbA1c< 7.0%
* Proportion of subjects with HbA1c< 7.0% without confirmed hypoglycaemic episodes during the last 12 weeks of treatment or within 7 days from last randomised treatment including only subjects exposed for at least 12 weeks
3. Self-measured plasma glucose measurements (SMPGs). The endpoints from the 8-point profiles (SMPG) include:
* 8-point profile
* Mean of the 8-point profile
* Prandial plasma glucose (PG) increment from 8-point profile
Key secondary safety endpoints
1. Incidence of treatment emergent adverse events (TEAEs)
2. Hypoglycaemia
a) Number of treatment emergent confirmed hypoglycaemic episodes both according to the Novo Nordisk definition for confirmed hypoglycaemic episodes (severe hypoglycaemia and/or a measured PG < 3.1 mmol/L (< 56 mg/dL)) as well as to The American Diabetes Association (ADA) definition ≤ 3.9 mmol/L (≤ 70 mg/dL)
b) Number of treatment emergent confirmed hypoglycaemic episodes in the maintenance period (from week 16 to end of trial including follow-up). The maintenance period has been defined for data collection purposes only
c) Number of treatment emergent nocturnal (00:01-05:59) confirmed hypoglycaemic episodes |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Key secondary efficacy endpoints:
1-3: At end of treatment (visit 28/26 weeks of treatment)
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Key secondary safety endpoints
1: During 28 weeks of trial
2: a) During 28 weeks of trial
b) From week 16 to end of trial including follow-up
c) During 28 weeks of trial
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Comparing two titration algorithms |
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E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 6 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Algeria |
Germany |
Malaysia |
Turkey |
United States |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | 5 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 10 |
E.8.9.2 | In all countries concerned by the trial days | 5 |